NIH Study Links Glucose metabolism to Alzheimer’s
The amyloid tangles and plaques that mark the signature of Alzheimer’s disease may be directly linked to abnormalities in how the brain breaks down glucose, says a new study supported by the National Institute on Aging (NIA), part of the National Institutes of Health.
The NIH researchers examined brain tissue from deceased participants in the Baltimore Longitudinal Study of Aging, measuring glucose levels in regions of the brain that are vulnerable to the disease and those that are not.
They analyzed three groups of BLSA participants: those with Alzheimer’s symptoms during life and with confirmed Alzheimer’s disease pathology (beta-amyloid protein plaques and neurofibrillary tangles) in the brain at death; healthy controls; and individuals without symptoms during life but with significant levels of Alzheimer’s pathology found in the brain post-mortem.
They found distinct abnormalities in glycolysis, the main process by which the brain breaks down glucose, with evidence linking the severity of the abnormalities to
the severity of Alzheimer’s pathology. Lower rates of glycolysis and higher brain glucose levels correlated to more severe plaques and tangles found in the brains of people with the disease. More severe reductions in brain glycolysis were also related to the expression of symptoms of Alzheimer’s disease during life, such as problems with memory.“For some time, researchers have thought about the possible links between how the brain processes glucose and Alzheimer’s,” said NIA Director Richard J. Hodes, M.D. “Research such as this involves new thinking about how to investigate these connections in the intensifying search for better and more effective ways to treat or prevent Alzheimer’s disease.”
The team tracked the brain’s usage of glucose by measuring ratios of the amino acids serine, glycine and alanine to glucose, allowing them to assess rates of the key steps of glycolysis.
They found that the activities of enzymes controlling these key glycolysis steps were lower in Alzheimer’s cases compared to normal brain tissue samples. Furthermore, lower enzyme activity was associated with more severe Alzheimer’s pathology in the brain and the development of symptoms.
“These findings point to a novel mechanism that could be targeted in the development of new treatments to help the brain overcome glycolysis defects in Alzheimer’s disease,” said Thambisetty.
The next steps for Thambisetty and his team include studying abnormalities in other metabolic pathways linked to glycolysis to determine how they may relate to Alzheimer’s pathology in the brain.